DESCRIPTION: The long-term objectives of this work are: 1) to understand the critical step in the ring-opening metabolism of the human carcinogen benzene to muconaldehyde; specifically, the intermediacy of a suspected compound termed "2,3-epoxyoxepin" will be investigated; 2) understanding of the role that substituted 2,3-epoxyoxepins may play in the ring-opening metabolism of other benzene derivatives including toluene and xylenes, and 3) confirming the hypothesis that the "2,3-epoxyoxepin paradigm" is the reason why eukaryotic cells apparently do not metabolically ring open polycyclic aromatic hydrocarbons (PAH) - a ubiquitous class of carcinogens. Benzene is a common environmental pollutant being present, for example, in percent levels in gasoline. The approach employed in the project presented herein is largely chemical. It involves synthesis and spectroscopic observations of 2,3-epoxyoxepin and simple derivatives which have not been previously isolated or even observed. The stability of these compounds will be analyzed to assess their potential in vivo lifetimes. Adducts will also be synthesized and used, in addition to label scrambling experiments, to see whether the epoxyoxepins are produced by microsomal enzymes. Stable 2,3-epoxyoxepins derivable from naphthalene (the simplest PAH) will be isolated. It is anticipated that the proposed study will shed light on the toxicity including carcinogenicity of benzene and related compounds.